**2. Oxidative stress in diabetes mellitus**

When the human's cells are perturbed by nutritional imbalance, infections, bacteria, toxins or disease reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed. ROS molecules are highly reactive and, the pathological consequence is damage to proteins, lipids and DNA [18, 19]. This oxidative damage may lead cell death and disease such as cancer or diabetes. Thus, oxidative stress may fi define as an imbalance between production of such reactive species and the body's ability to detoxify.

Diabetic subjects tend to have an increase in ROS generation and a decrease in antioxidant defenses [18–24], in this case oxidative stress is a response to glucose and/or lipid overload. Thus, oxidative stress is involved in the occurrence of complications in subjects with T2DM [20–24], and also affect the two major mechanisms failing during diabetes: insulin resistance and insulin secretion [25–28].

According to Giugliano et al. patients with diabetes present a high level of oxidative stress leads to the appearance of atherosclerosis [29]. Also, according to Ceriello, hyperglycemia generates oxidative stress, which leads to endothelial dysfunction in blood vessels [30]. Atherosclerotic disease is the most important and frequent macrovascular complication in diabetics and it means the chronic inflammation and injury to the arterial. Oxidized lipids accumulate in the endothelial wall of the arteries, and this accumulation can lead to acute vascular infarction [20].

The link between diabetes and oxidative stress was conducted by measuring certain biomarkers such as lipid peroxidation products, biomarker for protein oxidation or DNA damage biomarker. These biomarkers are the result of free radical's damage on lipids, proteins and DNA [18–20].

**151**

**3.2 Exhaled breath**

*Organic Volatile Compounds Used in Type 2 Diabetes DOI: http://dx.doi.org/10.5772/intechopen.94752*

an accelerated protein catabolism.

ethylene as breath biomarker [33].

**3.1 Overview of breath analysis**

**3. VOCs biomarkers in exhaled breath**

Responsible for oxidative stress is the attack on proteins induce by the reaction between ROS and some amino acids [24]. Proteins are the principal target of ROS causing protein glycation and oxidative degeneration. Therefore, glycated hemoglobin HbA1c measure the protein alteration and is considered as biomarker of oxidative stress [31]. Ammonia is a biomarker of protein metabolism, and at subjects with T2DM, insulin deprivation is associated with an increase in amino acids and by

In diabetes the lipid profile is modified thus leading to the occurrence of lipid peroxidation. Another target of free radicals are the polyunsaturated fatty acids in cell membranes [32]. The end-products of LP that can be used to measure the effects of free radicals on lipids are malondialdehyde (MDA) measured in blood and

Breath analysis can be considered as a potentially tool for the diagnosis and study of medical diseases. Respiratory analysis has been used in medicine since ancient times, from the time of Hippocrates (460–370 BC), when ancient Greek doctors assessing human health using human breath aroma [34–39]. The first breath analysis was conducted by Lavoisier in 1782, this showing that carbon dioxide from breathing is a product of combustion produced in the body [2, 38–40]. Respiratory studies continued later, when it was shown that human respiration contains VOCs, important in assessing human health [3–5]. The first invention that use gaseous compounds exhaled breath to assess human health was made in 1931 by Dr. Rolla N. Harger. He invented the 'drunkometer a breath-alcohol test, used to determine the alcohol concentration and has been widely used since 1938. An important step in breath analysis was conducted by Pauling et al. in 1971 when using a gas chromatograph were able to detect more than 200 VOCs in human breath [40]. Many studies on exhaled breath have been carried aiming to characterize these VOCs, and the studies carried out of Phillips estimated 1259 compounds in normal subjects in 1997 [41], and over 3000 compounds in 1999 [42]. The analysis of exhaled air is under investigation as a promising tool for express and noninvasive analysis of biochemical processes in the human body. The techniques currently used are promising to translate into clinics not for a specific disease diagnostic but more for providing information about biochemical processes that arise from underlying diseases. Nowadays, there are several commercially available devices for monitoring of breath biomarkers, such as 13C used to diagnose Helicobacter pylori [43], CH4 in breath accompanied by electrochemical sensors to detect H2 and O2 for diagnosis of gastrointestinal disorders [44], asthma detection by exhaled nitric oxide, breath alcohol testing [45], lung cancer detection [46], fructose malabsorption with hydrogen breath test, monitoring uptake of disinfection by-products following swimming [47] chronic kidney disease (CKD) and diabetes mellitus [48].

Human respiration is a gaseous mixture, and the main compounds are nitrogen, oxygen, carbon dioxide, inert gases, water vapor. In addition to these compounds that are found in high concentration in respiration, VOCs and inorganic molecules can also be found [49]. The presence of the latter in the composition of respiration depends on several external or internal factors. Thus, the composition of human

*Organic Volatile Compounds Used in Type 2 Diabetes DOI: http://dx.doi.org/10.5772/intechopen.94752*

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

in urban areas (310.3 million) [9, 10].

hyperglycemia in pregnancy in 2019) [9–14].

**2. Oxidative stress in diabetes mellitus**

damage on lipids, proteins and DNA [18–20].

with blood tests.

body's ability to detoxify.

disease, stroke, neuropathy, nephropathy, retinopathy [16, 17].

type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM). According to International Diabetes Federation (IDF) 1 of 11 adults (20–79 years) have diabetes (463 million people), 1 in 2 adults with diabetes are undiagnosed (232 million people) and 2 in 3 people with diabetes lives

Individuals with T2DM presents increased risk for microvascular and macrovascular complications due to hyperglycemia. The complications related to diabetes are: eye disease (diabetic retinopathy), cardiovascular disease (one-third do half of all are diabetes related deaths), kidney disease, oral, nerve and/or vascular damage and diabetic foot complications (diabetic foot and lower limb complications affect between 40 and 60 million people with diabetes globally), diabetes-related complications of pregnancy (approximately 20.4 million of live births were affected by

Studies over time have shown that oxidative stress contributes to the development and progression of diabetes, in T2DM particularly [15]. In diabetics, through hyperglycemia, hyperlipidemia, and hypertension is induced oxidative stress that affects multiple organs, leading to various complications including coronary artery

The aim of this chapter is showing the role of breath analysis in the evolution of type 2 diabetes mellitus by measuring ethylene and ammonia as oxidative stress breath biomarkers at T2DM and healthy subjects, using a CO2 laser photoacoustic spectroscopy (CO2LPAS) system. At the same time, it was determined the glycated hemoglobin HbA1c and blood glucose levels. Breath tests were compared between the two groups (healthy and with T2DM) to see if the breath analysis can discriminate between diabetic and healthy subjects, and if the breath tests are in accordance

When the human's cells are perturbed by nutritional imbalance, infections, bacteria, toxins or disease reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed. ROS molecules are highly reactive and, the pathological consequence is damage to proteins, lipids and DNA [18, 19]. This oxidative damage may lead cell death and disease such as cancer or diabetes. Thus, oxidative stress may fi define as an imbalance between production of such reactive species and the

Diabetic subjects tend to have an increase in ROS generation and a decrease in antioxidant defenses [18–24], in this case oxidative stress is a response to glucose and/or lipid overload. Thus, oxidative stress is involved in the occurrence of complications in subjects with T2DM [20–24], and also affect the two major mechanisms failing during diabetes: insulin resistance and insulin secretion [25–28]. According to Giugliano et al. patients with diabetes present a high level of oxidative stress leads to the appearance of atherosclerosis [29]. Also, according to Ceriello, hyperglycemia generates oxidative stress, which leads to endothelial dysfunction in blood vessels [30]. Atherosclerotic disease is the most important and frequent macrovascular complication in diabetics and it means the chronic inflammation and injury to the arterial. Oxidized lipids accumulate in the endothelial wall of the arteries, and this accumulation can lead to acute vascular infarction [20]. The link between diabetes and oxidative stress was conducted by measuring certain biomarkers such as lipid peroxidation products, biomarker for protein oxidation or DNA damage biomarker. These biomarkers are the result of free radical's

**150**

Responsible for oxidative stress is the attack on proteins induce by the reaction between ROS and some amino acids [24]. Proteins are the principal target of ROS causing protein glycation and oxidative degeneration. Therefore, glycated hemoglobin HbA1c measure the protein alteration and is considered as biomarker of oxidative stress [31]. Ammonia is a biomarker of protein metabolism, and at subjects with T2DM, insulin deprivation is associated with an increase in amino acids and by an accelerated protein catabolism.

In diabetes the lipid profile is modified thus leading to the occurrence of lipid peroxidation. Another target of free radicals are the polyunsaturated fatty acids in cell membranes [32]. The end-products of LP that can be used to measure the effects of free radicals on lipids are malondialdehyde (MDA) measured in blood and ethylene as breath biomarker [33].
